JP2011020004A - Method for producing microstructure, and microreactor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a microstructure, in which the microstructure which has the desired particle size and small variation in the particle size is produced in high production yield by using a combination of liquids that are brought into contact with each other so as to be reacted or solidified in a comparatively short time or by using three or more liquids, and to provide a microreactor. <P>SOLUTION: The method for producing the microstructure by using the microreactor including a main flow path and a plurality of subflow paths includes: a step of supplying a liquid to the main flow path; a step of supplying different liquids respectively to the plurality of subflow paths each having an outlet connected to the main flow path; and a step in which liquids to be supplied to the main flow path through the outlet of each of the plurality of subflow paths are supplied in a direction of substantially having an intersection point in a main fluid and brought into contact in laminar flow states. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a method for manufacturing a microstructure and a microreactor. More specifically, even in the case of manufacturing a microstructure using a combination of liquids such that liquids react and solidify in a relatively short time by contact, or using three or more types of liquids, the desired particle size size is maintained. In addition, the present invention relates to a method of manufacturing a microstructure having a small variation in particle size with a high yield, and a microreactor capable of easily manufacturing such a microstructure.

  In recent years, research on chemical reactions in microspaces using microreactors and microchannels has been extensively conducted. A microreactor and a microchannel are generic names of microreactors having microchannels of several micrometers to several hundreds of micrometers, (1) heating and cooling rates are fast, (2) the flow is laminar ( 3) The surface area per unit volume is large, and (4) The reaction proceeds rapidly because the diffusion length of the substance is short. Utilizing these features, a high-speed, highly selective reaction system that has never existed before can be constructed. Is possible.

  As an example synthesized by a microreactor, micrometer-order microparticles and microcapsules are used as colorant particles (colorant capsules) such as two-color balls such as inkjet inks, toner particles, and display display elements, as well as light diffusing agents, There are many uses such as drug delivery systems, food, heat storage materials, and microcapsules such as pressure sensitive paper, but these are required to be monodispersed with little variation in particle diameter.

  Regarding the synthesis of microparticles and microcapsules using a microreactor or microchannel, “Patent Document 1” describes the manufacturing method of a microstructure and the content of the microreactor. “Non-patent document 1” describes the production of calcium alginate gel having a particle size of 57 μm to 220 μm in oil. “Patent Document 2” describes a method for producing two-color phase-separated colored particles for electronic paper using microchannels.

In “Patent Document 1”, the first flow path and the second flow path are three-dimensionally merged to form a merge flow path, and at least a part having an outlet at the first flow path as an end portion is included. The first liquid and the second liquid are contacted in a laminar flow state at a point where the contents relating to the microreactor surrounded by the second flow path and the first flow path and the second flow path merge. And a method for manufacturing a microstructure is described. However, in the case of a combination of liquids that would react and solidify in a short time if the first liquid and the second liquid contact each other like a gelling agent and a gelation initiator, At the outlet of the first flow path, there is a problem that the flow path clogging is often caused by the reaction-solidified substance, or the flow path is closed in a severe case.
Further, when fine particles are synthesized using three or more kinds of liquids, there is a problem that the microreactor used in Patent Document 1 cannot be used.

  In “Non-patent Document 1”, a continuous phase flow path in which a sodium alginate aqueous solution and a calcium chloride aqueous solution are separately extruded from a micro nozzle into oil and the sodium alginate droplets and calcium chloride droplets do not contribute to the reaction is provided. It is described that a calcium alginate gel is formed by coalescence while flowing. However, the droplets pushed out from the micro nozzles are not surely united with one-to-one droplets, and those that do not coalesce or the same type of droplets coalesce. There was a problem that the particle size variation coefficient was not reduced as expected.

  On the other hand, in “Patent Document 2”, two colored continuous phases containing a polymerizable resin component are separately introduced into the first microchannel, the two colored continuous phases are joined and transferred, and the first microchannel is terminated. From the section, the colored continuous phase is sequentially discharged into the spherical particleized phase of the flowing medium flowing into the second microchannel, and the colored discharge is sequentially spheroidized while the second microchannel is being transferred, Describes a process for producing two-color phase-separated colored spherical polymer particles which are polymerized and cured by the method described above. However, while the two colored continuous phases are transported in the first microchannel, the two colors are mixed because the two color components move through the interface due to diffusion. There is a problem that the smaller the is, the more conspicuous the effect becomes.

JP2007-14936 JP2004 197083

Shinji Sugiura et al., “Particle Size Control of Calcium Alginate Beads Using a Micro Nozzle Array,” Chemical Engineering Symposium Series, Vol. 79, Page 42-45, (2006)

  The present invention has been made to solve the above-described conventional problems, and an object of the present invention is to form a microstructure having a desired shape by contacting a plurality of liquids and having a small size variation. It is an object of the present invention to provide a method for forming a body at a high yield and in a simple and inexpensive manner.

  As a result of intensive studies to achieve the above object, the present inventors have made a plurality of sub-channel liquids in a laminar flow state in the main channel liquid in the vicinity where the main channel and the plurality of sub-channels merge. It has been found that the above object can be achieved by bringing a physical process and / or chemical reaction instantaneously at the liquid-liquid interface by bringing them into contact with each other, and the present invention has been completed.

The microstructure manufacturing method of the present invention is a method for manufacturing a microstructure using a microreactor having a main channel and a plurality of sub channels.
Supplying liquid to the main flow path;
Supplying different liquids to a plurality of sub-channels having outlets in the main channel;
A step in which the liquid supplied from the outlets of the plurality of sub-channels to the main channel is supplied in a direction substantially having an intersection in the main fluid and contacts in a laminar flow state;
The manufacturing method of the microstructure characterized by including this.

  In a preferred embodiment, the number of lay nozzles in the laminar flow is 0.01 to 200.

  In a preferred embodiment, each of the flow rates of the plurality of sub-channel liquids is smaller than the flow rate of the main channel liquid.

  In a preferred embodiment, the liquids in the plurality of sub-channels are respectively contacted in discrete droplets or liquid mass states of the discontinuous fluid.

  In a preferred embodiment, the raw liquids in the plurality of sub-channels are supplied to the main channel in a pulsating manner or intermittently in a substantially synchronized manner.

  In a preferred embodiment, the main channel liquid is an incompatible liquid with the plurality of sub channel liquids.

In another aspect of the invention, a microreactor is provided. The microreactor of the present invention is a microreactor having a main flow path and a plurality of sub flow paths,
A plurality of sub-channels are installed so that the outlets of the plurality of sub-channels are in the side wall or the channel of the main channel, and the extension lines from the outlets of the plurality of sub-channels are in the main channel A microreactor characterized in that a plurality of sub-channels are installed so as to substantially intersect at one point.

  In a preferred embodiment, in the microreactor of the present invention, the inner diameters of the outlets of the plurality of sub-channels are 1 μm to 500 μm.

  In a preferred embodiment, the microreactor of the present invention includes pulse generation means for causing the plurality of liquids to flow in a pulsating manner through the plurality of sub-channels.

  In a preferred embodiment, the microreactor of the present invention includes a flow rate control means for varying the flow rate of the main liquid in the main flow path and the flow rates of the plurality of liquids in the plurality of sub flow paths.

  When the microstructure is manufactured using the microreactor according to the present invention, the following advantages can be obtained by bringing the sub-channel liquid into contact with the liquid in the main channel having a relatively large flow rate in a laminar flow state. It is done. : (1) If the combination of liquids introduced into a plurality of sub-flow channels comes into contact with each other like a gelling agent and a gelation initiator, the particles are a combination of liquids that will react and solidify in a short time When mixing is in progress, as in the case of synthesizing liquids, even if there is a combination of liquids that are defective, contact is made for the first time in the main flow path with a relatively large flow rate, so that the target microstructure can be obtained without problems such as clogging. (2) Since it is a reaction at the liquid-liquid interface in a minute space, a very stable and precise reaction is realized, and the uniformity of the resulting microstructure is extremely excellent; (3) Three types Fine particles can be synthesized using the above liquid. (4) It is possible to manufacture a microstructure having a desired size and a desired composition by changing the flow path and the supply form and flow rate of the introduction liquid; examples of the microstructure obtained in the present invention include: , Spherical fine particles, irregular fine particles, microcapsules, microfibers, microlots and the like.

It is a schematic sectional drawing along the flow-path direction of the apparatus (microreactor) 100 which can be preferably used for the manufacturing method by preferable embodiment of this invention, (b) is sectional drawing of a confluence | merging part. (A) is the schematic seen from the upper direction of the apparatus 100, (b) is the elements on larger scale of the confluence | merging part vicinity of Fig.2 (a). It is the elements on larger scale of Drawing 2 (a) showing a preferred embodiment in the case of producing fine particles with the microreactor of the present invention. It is the schematic which shows preferable embodiment of the pulse generation means in the microreactor of this invention. 4 is an observation photograph of calcium alginate particles obtained in Example 2 of the present invention. 10 shows a process for forming an acrylic twist ball by photographing with a video camera of Example 4 of the present invention.

Hereinafter, although preferable embodiment of this invention is described, this invention is not limited to these embodiment.
First, a more preferred embodiment of the microreactor of the present invention will be described with reference to the drawings.
FIG. 1A is a schematic cross-sectional view of a device (microreactor) 100 that can be preferably used in a manufacturing method according to a preferred embodiment of the present invention along the flow direction, and FIG. It is sectional drawing of the merge part of a subchannel. FIG. 2A is a schematic view of the apparatus 100 as viewed from above, and FIG. 2B is an enlarged view of the vicinity of the merging portion in FIG. 10 main flow paths surround the outlet portions of 20 sub-flow paths, and the main flow path merges with the sub-flow paths in a three-dimensional manner at 31 merge points, followed by 30 merge flow paths. Yes. FIG. 3 is a partially enlarged view of FIG. 2 (a) showing a preferred embodiment in the case where fine particles are produced by the microreactor of the present invention. Forty droplets or liquid masses coming out from the two sub-channels into the main channel collide with each other in the liquid in the main channel after joining, and 41 droplets or liquid masses are united.

  In one embodiment, the total length L of the reactor is about 30 mm to about 60 mm. The diameter of the main channel (when the cross-sectional shape viewed from the channel direction is substantially circular) is 20 μm to 1500 μm, more preferably 50 μm to 1000 μm, and still more preferably 150 μm to 750 μm.

  In the microreactor of the present invention, the inner diameter of the outlet of the sub flow channel is preferably 1 μm to 500 μm, more preferably 5 μm to 300 μm, and further preferably 10 μm to 150 μm. The smaller the inner diameter of the channel outlet, the smaller droplets or liquid lumps are discharged into the liquid in the main channel and smaller particles can be synthesized, but the channel resistance is inversely proportional to the fourth power of the channel diameter. The pressure loss becomes a big problem. When the inner diameter of the outlet of the sub-channel is within the above range, the desired particle size in the market can be synthesized while avoiding the problem of pressure loss. Further, the sub-channel outlet portion may be manufactured by stereolithography, and can be formed by inserting or inserting any appropriate material. Preferably, it can be formed of epoxy resin, stainless steel, alumina ceramics, nickel, glass, SiO2, or the like.

  Any appropriate surface treatment can be applied to the peripheral wall of the sub-channel outlet. When the raw material liquid in the sub-channel is a hydrophilic liquid, water repellent treatment is preferable. As the water repellent used in the water repellent treatment, a water repellent containing any appropriate resin is employed. When the raw material liquid in the sub-channel is a lipophilic liquid, it is preferably a hydrophilic agent.

  The microreactor of the present invention preferably has an intersection substantially on an extension line from the outlet in the plurality of sub-channels, and the intersection exists in the main channel after merging (downstream of the merging point). Become. According to the above configuration, the liquids that have come out of the sub flow paths to the main flow path can be contacted and united in the main flow path after being joined together in a spatially reliable manner. In this case, the droplet or liquid mass from the sub-channel has a substantial size, and it is sufficient that the liquid including the size can be contacted and united with each other. Also, if you do not want to mix as much as possible when the droplets or liquid masses coming out from the sub flow channel into the main flow channel make contact or coalescence, increase the distance from the confluence to the contact point and further Slow down the flow rate of the liquid and make the impact small. When mixing is desired as much as possible at the time of contacting and joining, the distance from the joining point to the contact point is made closer, the flow rate of the sub-channel liquid is increased, and the impact is brought into contact or collides greatly.

  For example, as shown in FIG. 4, the microreactor of the present invention is provided with a pulse generating means 50 for causing a liquid to flow in a sub-flow path. The position of the pulse generating means 50 may be anywhere as long as it is in the middle of the sub flow path, and can be appropriately designed according to the purpose. By synchronizing the timing and time of applying the pulsed pressure in the plurality of sub-channels, the droplets or liquid masses coming out from the outlets of the plurality of sub-channels to the main channel can be contacted in a timely manner. It becomes possible. Further, by controlling the pulse waveform shape, the diameter and shape of the obtained microstructure can be controlled. An example of the pulse pressure generating means is an electromagnetic valve manufactured by Jupiter Corporation (part number INKX0514100A). By opening and closing the valve with pressure applied by a syringe pump, it is possible to generate pulsed pressure in the liquid. The frequency for opening and closing the valve is preferably 1 to 1000 Hz, more preferably 1 Hz to 50 Hz.

  The microreactor of the present invention may be provided with a flow rate control means for varying the flow rate of the liquid in the main flow path 10 and the flow rate of the liquid in the sub flow path. Examples of the flow rate control means include a syringe pump, a plunger pump, and a gear pump. A syringe pump is preferable. By providing the flow rate control means, the liquid flow rate in the main flow channel 10 and the liquid flow rate in the sub flow channel can be varied, so that the diameter of the obtained microstructure can be arbitrarily controlled.

  The microreactor of the present invention may be produced by any method, but it is preferably produced by an optical modeling method in that it can be produced easily and accurately. The stereolithography method converts a 3D image designed with 3D CAD data into 2D slice data, and based on this data, the photocurable resin is cured layer by layer with a laser and laminated in 3D. It is a method of modeling. More specifically, a three-dimensional image designed with three-dimensional CAD data is sliced into thin layers of several layers and converted into two-dimensional slice data. Based on this two-dimensional slice data, the laser is inside the tank. The cross-sectional shape is drawn by scanning the surface of the photocurable resin. The portion irradiated with the laser is cured, and a cross-section for one layer is formed on the elevator. After that, the elevator descends one layer at a time, and several thin cross-sectional bodies are continuously laminated and three-dimensionally layered. Finally, by lifting the elevator, a three-dimensional layered model is taken out and subjected to post-processing to be completed. As an optical modeling apparatus that can be used for the optical modeling method, for example, an optical modeling apparatus (for example, SCS-1000HD) manufactured by Deemec Co., Ltd. may be used. Examples of the photocurable resin that can be used in the optical modeling method include a photocurable resin manufactured by Deemec Co., Ltd. (for example, oxetane-based SCR950 manufactured by JSR, etc.). Examples of the laser include a He—Cd laser (peak wavelength = 325 nm). For example, the laser spot size is preferably φ10 to 100 μm, and more preferably φ30 to 70 μm. The thickness of one resin layer obtained by curing is preferably, for example, 10 to 50 μm, and more preferably 20 to 40 μm.

A method for manufacturing a microstructure according to a preferred embodiment of the present invention is a method for manufacturing a microstructure using a microreactor including a main channel 10 and a plurality of sub-channels 20, and supplying liquid to the main channel And a step of supplying different liquids to the plurality of sub-channels, and a layer of the liquid supplied to the plurality of sub-channels in the main liquid in the vicinity of the merge of the main channels and the sub-channels. A step of contacting in a flow state.
In the present invention, by using the apparatus as described above, the liquid in the main flow path and the liquid in the sub flow path form a laminar flow at the merge point 31 and the merge flow path 30, and a plurality of sub flow path liquids are formed. Contact in the main channel liquid. That is, in the present invention, the liquids in the plurality of sub-channels come into contact in a laminar flow state in the liquid in the main channel. The liquid in the sub channel can be appropriately selected according to the purpose. By bringing the liquids in the sub-channels into contact with each other in the liquid in the main channel in a laminar flow state, it is possible to manufacture a microstructure without problems such as clogging of the outlet portion of the sub-channels.

  The laminar flow Reynolds number is preferably 0.01 to 200, more preferably 0.1 to 50, and particularly preferably 0.5 to 20. With such a very small number of lay nozzles, droplets that emerge from the sub-channel to the main channel can be controlled by controlling the flow rate of the sub-channel and the main channel in a very stable laminar flow space. Alternatively, the size of the liquid mass can be arbitrarily controlled, and the liquid droplets or the liquid mass coming out of the sub-flow path can be reliably brought into contact with each other. Is monodisperse and its size can be controlled.

  Preferably, each of the flow rates of the plurality of sub flow channels is smaller than the flow rate of the main flow channel. According to the above configuration, the liquids that have come out of the sub flow channel to the main flow channel are in contact with each other, and since the contacted liquid has the main flow channel liquid with a large flow rate, It is difficult to contact the left and right walls, and is less susceptible to adverse effects such as wall friction, microstructure deformation, coalescence, and channel blockage. Although depending on the size of each channel, the flow rate of the main channel is preferably 10 μl / min to 1000 μl / min, and the flow rate of one sub-channel is preferably 0.5 μl / min to 50 μl. / Min.

  Preferably, the raw liquids in the plurality of sub-channels are brought into contact with each other in the form of discrete droplets or liquid masses of the discontinuous fluid. According to said structure, since the raw material liquid of each subchannel is made to contact in the discrete droplet state or liquid mass state of a discontinuous body, the individual liquids of each subchannel are reliably made to contact at a predetermined ratio. It becomes possible. Also, if the sub-channel liquid is incompatible with the main channel liquid (for example, the main channel liquid is an oil-based solvent, the sub-channel liquid is an aqueous solvent, etc.) after contact, On the other hand, it becomes a droplet or liquid mass of a discontinuous material again, and mixing and reaction are possible in a small space of individual droplets or liquid mass.

  Preferably, the raw material liquids in the plurality of sub flow paths are supplied to the main flow path in a pulsating or intermittent manner substantially in synchronization. According to the above configuration, since the timing and interval of the individual liquid droplets or liquid masses of the liquids coming out from the plurality of sub-channels to the main channel are the same, the liquids are reliably contacted in time. , Can be united. Strictly speaking, since the droplets or the liquid mass has a certain size, it is possible to allow a time shift in which the liquid droplets or the liquid mass can contact and merge with each other. In this case, the liquid flow in the sub flow path does not necessarily have to be pulsating or intermittent. For example, if the liquid in the sub flow path and the liquid in the main flow path are incompatible, the sub flow The liquid coming out of the channel into the main channel becomes pulsating or intermittent due to the interfacial tension. Moreover, in order to substantially synchronize, the timing of liquid feeding of each sub flow path (even if pulsating liquid feeding or continuous flow liquid feeding, the liquid feeding pump uses a motor to generate micro pulsation. Adjust the case). In addition, considering the factors that liquid response time cannot be ignored, such as the flow resistance of the sub flow path, the liquid capacity of the sub flow path, the damping capacity of the sub flow path, and the flow resistance of the sub flow path outlet, A drive signal of a liquid supply source such as a pump or a pulsation mechanism is adjusted so that the liquid coming out from the passage outlet to the main flow path is synchronized.

Preferably, the main channel liquid is an incompatible liquid with the plurality of sub channel liquids.
According to the above configuration, the liquid that emerges from the plurality of sub-channels into the main channel becomes a droplet having a spherical shape or a shape close to a sphere due to the interfacial tension. Further, due to the omnidirectional shear force from the laminar flow state and the main flow, so-called monodispersed droplets having very uniform sizes are obtained. The combination of the main channel liquid and the sub channel liquid may be a compatible combination. In this case, a liquid mass close to the shape of the sub channel outlet is obtained.
Moreover, the flow velocity of each flow can arbitrarily control the droplet or liquid mass size, and can also control the mixing state of the liquid droplets or liquid mass. If the ratio of the flow rate of the sub flow channel to the flow rate of the main flow channel “main flow rate / sub flow rate” is large, the shear force is relatively large, the droplet or liquid mass is small, and if the “main flow rate / sub flow rate” is small, The shearing force becomes relatively weak, and the droplet or liquid mass becomes large. As for the mixing state, if the “main flow rate / sub flow rate” is large, the contact point of the droplets or liquid mass shifts to the downstream side after merging, and there is little impact between the droplets or liquid mass at the time of contact, and mixing is difficult. However, if the “main flow rate / sub flow rate” is small, the speed at the time of contact is high and the contact point is immediately after joining, so that the impact of the droplets or liquid masses at the time of contact is large and easy to be mixed.

  In the present invention, the type of the main channel liquid and each sub channel liquid is appropriately selected, and / or the flow rate of the main channel liquid and the sub channel liquid is appropriately selected, and / or By performing an appropriate chemical treatment or surface treatment, a capsule microstructure or a porous microstructure other than the spherical microstructure can be obtained.

  Examples of combinations of the main channel liquid and the sub channel liquid in the present invention include, for example, 1) the main channel liquid is a vegetable lipophilic solvent, one sub channel liquid is a polyanion solution, and the other sub channel liquid Is a polycation solution, 2) the main channel liquid is a vegetable lipophilic solvent, one sub-channel liquid is a pH adjusting solution such as an aqueous solution of sodium silicate and hydrochloric acid, and 3) the main channel liquid is a vegetable lipophilic solvent. One sub-channel liquid includes a chloroauric acid solution, and the other sub-channel liquid includes a reducing agent. The case of 1) is a typical example of microcapsule synthesis utilizing a polyelectrolyte reaction, the case of 2) is a typical example of inorganic particle synthesis utilizing a sol-gel reaction, and the case of 3) is a liquid phase reduction method. This is a representative example of synthesis of precious metal particles used.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these Examples. The particle diameter and CV value of the particles obtained in each example were measured by the following methods.
Particle size and CV
The obtained particles were observed with a microscope (manufactured by Keyence) and measured for length.
It was measured with a viscosity vibration viscometer (VISCOMATE VM-1G).
The contact angle was measured with a contact angle meter (DM-500, manufactured by Kyowa Kagaku).

For the microreactor shown in Figs. 1 to 3, a stereo image designed with 3D CAD data is sliced into several thin cross-sections using an optical modeling device (trade name: SCS-1000HD, manufactured by DEMEC Co., Ltd.) And converted into two-dimensional slice data. A photo-curing resin (manufactured by JSR, trade name: SCR950 oxetane) and an elevator are placed in the tank, and a laser (He-Cd laser, peak wavelength = 325 nm) is placed in the tank based on the two-dimensional slice data. A cross-sectional shape was drawn by scanning the surface of the photocurable resin. The laser spot size was φ50 μm, and the laser scan pitch was φ30 μm. The portion irradiated with the laser was cured, and a cross section for one layer (thickness for one resin layer = 30 μm) was formed on the elevator. After that, the elevator descended one layer at a time, and several thin cross-sections were continuously laminated and three-dimensionally layered. Finally, by lifting the elevator, a three-dimensional layered model was taken out and post-processed to complete the microreactor shown in FIGS.

(Preparation of sodium alginate aqueous solution)
1 g of sodium alginate was added little by little to 99 g of ion-exchanged water and stirred to prepare a 1 wt% aqueous sodium alginate solution. The viscosity of the obtained aqueous sodium alginate solution was 54.3 Pa · s, and the contact angle with the flow path was 71 °.
(Preparation of calcium chloride aqueous solution)
1 g of calcium chloride was added little by little to 99 g of ion-exchanged water and stirred to prepare a 1 wt% (about 0.1 N) calcium chloride aqueous solution. The obtained aqueous solution of calcium chloride had a viscosity of 2.1 Pa · s and a contact angle with the flow path of 75 °.
(Synthesis of alginate balls)
The aqueous sodium alginate solution obtained above was passed through one sub-channel of the microreactor, the aqueous calcium chloride solution was flowed through the other sub-channel, and soybean oil was flowed through the main channel. The viscosity of soybean oil was 55.7 Pa · s, and the contact angle with the flow path was 7.8 °. The inner diameters of the outlets of the first and second channels, which are sub-channels, were both 50 μm, and the inner diameter of the main channel was 600 μm. All three types of liquids were rectified using a syringe pump, the flow rates of both the sodium alginate aqueous solution and the calcium chloride aqueous solution were 8.3 μl / min (flow rate 70.6 mm / sec), and the soybean oil flow rate was 100 μl / min ( The flow rate ratio between the sub flow channel and the main flow channel was 1: 6 (flow rate ratio was 12: 1). Near the confluence, the droplets of the sodium alginate aqueous solution and the calcium chloride aqueous solution contacted and joined and reacted to obtain calcium alginate particles. The obtained calcium alginate particles had an average diameter of 105.5 μm and a coefficient of variation (CV) of 3.7%.

(Synthesis of alginate balls)
The flow rates of the sodium alginate aqueous solution and the calcium chloride aqueous solution are both 20.8 μl / min (flow rate 176.8 mm / sec), and the soybean oil flow rate is 100 μl / min (flow rate 5.9 mm / sec). In addition, calcium alginate particles were obtained in the same manner as in Example 2 except that the flow rate ratio between the second channel and the main channel was 1: 2.4 (flow rate ratio was 30: 1). The obtained calcium alginate had an average diameter of 145.3 μm and a coefficient of variation (CV) of 3.2%.

(Preparation of thermosetting acrylic monomer liquid)
100 parts by weight of distilled water is added to 100 parts by weight of ACMO (manufactured by Kojin Co., Ltd.), and thermal polymerization initiator 2,2-azobis (2-methylpropionamide) dihydrochloride (V-50) (manufactured by Wako Pure Chemical Industries, Ltd.) 3 parts by weight and 10 parts by weight of a crosslinking agent ethylene glycol diglycidyl ether (manufactured by Tokyo Chemical Industry Co., Ltd.) were added to prepare a thermosetting acrylic monomer liquid. The viscosity of the obtained monomer liquid was 3.58 Pa · s, and the contact angle with the flow path was 50.3 °.
A red monomer liquid was added by adding 2 parts by weight of Allura Red (red No. 40) to the obtained monomer liquid, and a blue monomer liquid was prepared by adding 2 parts by weight of Acid Blue 9 (blue No. 1).
(Preparation of soybean oil solution)
1 g of sorbitan monooleate (Span 80) was added to 99 g of soybean oil and stirred to prepare a soybean oil solution. The resulting soybean oil solution had a viscosity of 59.3 Pa · s and a contact angle with the flow path of 7.5 °.
(Synthesis of acrylic two-color balls)
The red monomer solution prepared above was passed through the sub-channel first channel of the microreactor, the blue monomer solution was flowed through the second channel of the sub-channel, and the soybean oil solution was flowed through the main channel. The inner diameter of the outlet of the first channel and the second channel of the sub-channel was 50 μm, and the inner diameter of the main channel was 600 μm. All three liquids were rectified using a syringe pump. The flow rates of the two color monomer liquids are both 8.3 μl / min (flow rate 70.6 mm / sec) and the soybean oil solution flow rate is 100 μl / min (flow rate 5.9 mm / sec). The flow rate ratio between the second flow channel and the main flow channel was 1: 6 (the flow rate ratio was 12: 1). The red and blue liquid droplets contacted at the junction of the three liquids to obtain twisted liquid droplets. The droplets were collected in a container containing the soybean oil solution obtained above heated to 90 ° C. at the outlet of the microreactor and polymerized with weak stirring to obtain an acrylic twist ball. The obtained acrylic twist ball had an average diameter of 168 μm and a coefficient of variation of 4.9%.

(Synthesis of acrylic two-color balls)
The inner diameter of the outlet of the first channel and the second channel of the sub channel is 40 μm, the flow rate of the two color monomer liquids is 4.1 μl / min (flow rate 35.3 mm / s), and the soybean oil solution Other than setting the flow rate to 400 μl / min (flow rate 23.6 mm / second) and the flow rate ratio of the first and second flow channels to the main flow channel to 1:12 (flow rate ratio is 3: 2). Obtained an acrylic twist ball in the same manner as in Example 3. The resulting acrylic twisted ball had an average diameter of 70.6 μm and a coefficient of variation of 6.2%.

  Since the production method of the present invention is very safe and highly accurate, it can be widely used in various chemical industries.

DESCRIPTION OF SYMBOLS 100 Microreactor 10 Main flow path 20 Sub flow path 30 Merge flow path 31 Merge point 40 Sub flow path Liquid droplets or liquid mass contact / merging 50 Pulse generation means 101 Supply port 102 to main flow path Sub flow path Supply port to

Claims (10)

Supplying a liquid to the main flow path in a method of manufacturing a microstructure using a microreactor having a main flow path and a plurality of sub flow paths;
Supplying different liquids to a plurality of sub-channels having outlets in the main channel;
A step in which the liquid supplied from the outlets of the plurality of sub-channels to the main channel is supplied in a direction substantially having an intersection in the main fluid and contacts in a laminar flow state;
The manufacturing method of the microstructure characterized by including this.   The manufacturing method of Claim 1 whose Reynolds number of the said laminar flow is 0.01-200.   The manufacturing method according to claim 1 or 2, wherein each of the flow rates of the plurality of sub-channel liquids is smaller than the flow rate of the main channel liquid.   The manufacturing method according to any one of claims 1 to 3, wherein the liquids in the plurality of sub-channels are brought into contact with each other in a discrete droplet state or a liquid mass state of the discontinuous fluid.   The manufacturing method according to claim 1, wherein the liquid in the plurality of sub-channels is supplied to the main channel in a pulsating manner or intermittently in a substantially synchronized manner.   The manufacturing method according to claim 1, wherein the main channel liquid is an incompatible liquid with the plurality of sub channel liquids. A microreactor having a main flow path and a plurality of sub flow paths,
A plurality of sub-channels are installed so that the outlets of the plurality of sub-channels are in the side wall or the channel of the main channel, and the extension lines from the outlets of the plurality of sub-channels are in the main channel A microreactor characterized in that a plurality of sub-channels are installed so as to substantially intersect at one point.   The microreactor according to claim 7, wherein an inner diameter of the outlet of each of the plurality of sub-channels is 1 μm to 500 μm.   The microreactor according to claim 7 or 8, comprising a pulse generation means for causing the plurality of liquids to flow in a pulsating manner through the plurality of sub-channels. 10. The microreactor according to claim 7, further comprising a flow rate control unit configured to vary a flow rate of the liquid in the main flow channel and a flow rate of the plurality of liquids in the plurality of sub flow channels.